In spite of its long history of use, several important aspects of nitroglycerin pharmacology and toxicology have not been elucidated. Quantitative studies on the oral and lung absorption of nitroglycerin have not been systematically carried out because of the lake of a sensitive analytical procedure capable of assaying nanogram/ml levels of nitroglycerin in biological fluids. Our continuing work on nitroglycerin recently leads to the development of a gas chromatographic method with a sensitivity down to 0.1 ng/ml plasma. This capability offers us a unique opportunity to conduct studies which will delineate some of the factors affecting oral and lung absorption of nitroglycerin in experimental animals. Oral absorption studies are designed to investigate the effect of oral dose, age, diet and co-administration of other organic nitrates on the rate and extent of absorption of intact nitroglycerin. Inter-animal variability in oral absorption will be examined in relation to the individual liver organic nitrate reductase activity responsible for first-pass metabolism. Lung absorption characteristics will be studied using (i) a modified Schanker method and (ii) nitroglycerin vapor exposure. The inter-relationship between tolerance development and environmental vapor and plasma levels of nitroglycerin will be examined. Knowledge gained from the proposed studies will no doubt contribute significantly to better therapeutic use and toxicological evaluations of nitroglycerin.